Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. 4. Further investigation on the inner spacer.
Novel multi-target-directed ligands were designed by replacing the inner dipiperidino function of 3 with less flexible or completely rigid moieties to obtain compounds endowed with multiple biological properties that might be relevant to Alzheimer's disease. 15 was the most interesting, inhibiting AChE in the nanomolar range and inhibiting AChE-induced and self-promoted beta-amyloid aggregation in the micromolar range.
Tumiatti
Vincenzo
V
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. vincenzo.tumiatti@unibo.it
Milelli
Andrea
A
Minarini
Anna
A
Rosini
Michela
M
Bolognesi
Maria Laura
ML
Micco
Marialuisa
M
Andrisano
Vincenza
V
Bartolini
Manuela
M
Mancini
Francesca
F
Recanatini
Maurizio
M
Cavalli
Andrea
A
Melchiorre
Carlo
C
D000110:Acetylcholinesterase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D008024:Ligands; D011073:Polyamines; D000110:Acetylcholinesterase